BMAL1 regulates -induced skin inflammation via REV-ERBα in mice.

Acne vulgaris is a common skin disease, affecting over 80% of adolescents. Inflammation is known to play a central role in acne development. Here, we aimed to investigate the role of the central clock gene in acne-associated inflammation in mice. To this end, mice were injected intradermally with () to induce acne-associated skin inflammation. We found that and its target genes and were down-regulated in the skin of -treated mice, suggesting a role of in the condition of acne. Supporting this, -deleted or jet-lagged mice showed exacerbated -induced inflammation in the skin. Regulation of -induced inflammation by was further confirmed in RAW264.7 cells and primary mouse keratinocytes. Transcriptomic and protein expression analyses suggested that regulated -induced inflammation via the NF-κB/NLRP3 axis, which is known to be repressed by REV-ERBα (a direct target of BMAL1). Moreover, loss of in mice exacerbated -induced inflammation. In addition, silencing attenuated the inhibitory effects of on -induced inflammation. knockdown failed to modulate -induced inflammation in -silenced cells. It was thus proposed that restrained -induced skin inflammation via its target REV-ERBα, which acts on the NF-κB/NLRP3 axis to repress inflammation. In conclusion, disruption is identified as a potential pathological factor of acne-associated inflammation. The findings increase our understanding of the crosstalk between skin clock and acne and suggest targeting circadian rhythms as a promising approach for management of acne.